The invention relates to time-of-flight mass spectrometers with orthogonal ion injection to which the ions are fed by an RF ion guide. The mass-dependent speed of the ions means that they undergo mass discrimination when injected into the pulser of the time-of-flight mass spectrometer.
Time-of-flight mass spectrometers that pulse a primary ion beam orthogonally to its original flight path into a drift tube are termed OTOF (orthogonal time-of-flight mass spectrometers). FIG. 1 illustrates such an OTOF. They have a so-called pulser (12) at the beginning of the secondary flight path (20) which accelerates a section of the primary ion beam, i.e. a fine string-shaped ion package, into the flight path at right angles to the previous original direction of the beam. This forms a band-shaped secondary ion beam (19) comprising individual string-shaped ion packages for the ions of different masses wherein light ions fly quickly and heavier ions fly more slowly. The direction of flight of this band-shaped secondary ion beam is between the previous original direction of the primary ion beam and the direction of acceleration at right angles to this. Such a time-of-flight mass spectrometer is preferably operated with a velocity-focusing reflector (13) which reflects the whole width of the band-shaped secondary ion beam (19) with the string-shaped ion packages and directs it toward a flat detector (14).
The term “mass” here always refers to the “mass-to-charge ratio” or “charge-related mass” m/z, which alone is of importance in mass spectrometry, and not simply to the “physical mass” m. The number z indicates the number of elementary charges, i.e. the number of excess electrons or protons of the ion, which act externally as the ion charge. All mass spectrometers without exception can measure only the mass-to-charge ratio m/z, not the physical mass m itself. The mass-to-charge ratio is the mass fraction per elementary ion charge. The terms “light” and “heavy” ions here are analogously understood as being ions with low or high charge-to-mass ratio m/z respectively. The term “mass spectrum” always relates to the “mass-to-charge ratios” or “charge-related masses” m/z.
The pulser (12) usually operates at 10 to 20 kilohertz. If one considers a time-of-flight mass spectrometer which operates at 16 kilohertz, 16,000 individual mass spectra are thus scanned per second, said spectra being digitized in a transient recorder and added to form sum spectra. The time for which spectra are added can be set. The time for additions can take a twentieth of a second, in which case around 800 individual mass spectra can be integrated to form a sum spectrum. The addition can also be carried out over ten seconds and encompass 160,000 individual mass spectra in the sum spectrum. This latter sum spectrum then has a very high dynamic measuring range for the ions in the spectrum.
The ions whose mass spectrum is to be measured are not generally a homogeneous ion species but rather a mixture of light, medium and heavy ions. The mass range here can be very broad: in protein digest mixtures, for example, the mass range of interest extends from individual amino acid ions up to peptides with around 40 amino acids, i.e. from a mass of about 50 Daltons to around 5,000 Daltons.
In the time-of-flight mass spectrometer in FIG. 1, the ions of a primary ion beam are extracted from an RF ion guide (10) with the aid of a lens system (11) and injected with a low kinetic energy of only around 20 electron-volts into the emptied pulser (12).
The filling process of the pulser, by injecting the ions, discriminates the ions according to mass. If this filling process of the pulser (12) is stopped after a short time by pulsing out the ions into the flight path (20), the very light ions have already reached the end of the pulser (12), medium-mass ions have only penetrated a short way into the pulser (12), while heavy and hence slow ions have not even reached the pulser (12). The pulse-ejected ion beam (19) thus contains only light and a few medium-mass ions. There are no heavy ions at all. For a very long injection time, on the other hand, during which the heavy ions have penetrated to the end of the pulser (12), these heavy ions are predominant in the pulse-ejected ion beam (19) since the high speed of the medium-mass and light ions means that most of them have already left the pulser (12) at the other end.
For each selected mass range of the mass spectrum there is thus an optimum starting time and an optimum duration for the injection process, the principle of which is already familiar from U.S. Pat. No. 6,285,027 B1 (I. Chernushevich and B. Thompson). A preferred mass range can be set using the starting time and duration of the injection into the pulser, which can be controlled by electric switching of the lens system (11). The energy of the injected ions basically represents a further optimization parameter; this energy of the injected ions, however, is usually not adjustable, or only within very narrow limits, because it is fixed by the geometry of the time-of-flight mass spectrometer, particularly by the distance between pulser (12) and detector (14).
The method of injecting the ions into the pulser at a given energy must be optimized not only with respect to starting time and duration. It is also necessary to generate a fine ion beam of optimum width so that the time-of-flight mass spectrometer has a high resolution. If all ions fly one behind the other precisely in the axis of the pulser (12), and if the ions have no velocity components transverse to the primary ion beam, then theoretically, as can be easily understood, an infinitely high mass resolution can be achieved because all ions of the same mass fly as an almost infinitely thin, string-shaped ion package precisely in the same front and impact onto the detector (14) at precisely the same time. If the primary ion beam (and hence the string-shaped ion package) has a finite cross section, but no ion has a velocity component transverse to the direction of the beam, it is again theoretically possible to achieve an infinitely high mass resolution by space focusing the pulser (12) in the familiar way. The high mass resolution can even be achieved if there is a strict correlation between the location of the ion (measured from the axis of the primary beam in the direction of the acceleration) and the transverse velocity of the ion in the primary beam in the direction of the acceleration. If no such correlation exists, however, i.e. if the locations of the ions and the transverse velocities of the ions are statistically distributed with no correlation between the two distributions, then it is not possible to achieve high mass resolution.
In addition to optimizing the injection process with respect to the mass range of the ions supplied, it is thus also necessary to condition the primary ion beam with respect to its spatial and velocity distribution in order to simultaneously achieve both a high mass range with low mass discrimination and a high mass resolution in the time-of-flight mass spectrometer. To condition the ion beam in this way, ions must be extracted which have been largely collisionally cooled in a neutral collision gas to achieve a very fine beam from the axis of the ion guide (10), and the extraction must be performed by a very good lens system (11).
Ion guides such as the guide (10) generally take the form of multipole RF rod systems filled with collision gas. The ions lose their kinetic energy in collisions with the collision gas and collect in the minimum of the pseudopotential, i.e. in the axis of the rod system. This process is called “collisional focusing”. The pseudopotential minimum for light ions is more pronounced and steeper than for heavy ions, so the light ions collect precisely in the axis and the heavier ions more to the outside, kept apart by the Coulomb repulsion of the light ions, as schematically represented in FIG. 2a. 
If an ion guide is used as an ion storage device which is not continuously refilled, and if the ions are extracted close to the axis in order to generate a fine ion beam, then a further mass discrimination occurs. The light ions, which are close to the axis, are extracted first; the heavier ions are extracted only when the light ions have been exhausted. When the lighter ions have been removed, the heavier ions automatically replace them close to the axis, as shown in FIGS. 2b and 2c. The effect is particularly large when a quadrupole rod system is used, which has the most pronounced pseudopotential minimum of all multipole rod systems. On the other hand, the finest beam cross section can be produced by a quadrupole rod system, which in turn means that the time-of-flight mass spectrometer demonstrates its best mass resolution.
If, by contrast, an ion storage device is continuously filled with ions, primarily light ions are continuously extracted. The heavy ions suffer a high degree of discrimination. If the rate of filling the ion storage device is very high, it is possible that the heavy ions are not extracted at all but are lost in the ion storage device. To reduce this disadvantage slightly, modern time-of-flight mass spectrometers normally use hexapole rod systems, but these have a slight disadvantage with respect to the mass resolution.
The objective of the invention is to provide an operating method for a time-of-flight mass spectrometer with orthogonal ion injection which has only minimal mass discrimination and where good ion utilization makes it possible to scan spectra with high mass resolution over a broad mass range. A suitable time-of-flight mass spectrometer is also to be provided.